Susceptibility of Pneumocystis to Echinocandins in Suspension and Biofilm Cultures
Open accessAbstract
The targeted inhibition of cyst but not trophic development by anidulafungin, caspofungin, and micafungin on Pneumocystis murina and Pneumocystis carinii in rodent models of Pneumocystis carinii pneumonia (PCP) was recently reported by us (M. T. Cushion et al., PLoS One 5:e8524, 2010). To better understand the effects of echinocandins on P. carinii , the same three compounds were evaluated in standard suspension and biofilm cultures supplemented with various concentrations of sera using the measurement of ATP as the indicator. In suspension cultures with 1 and 5% serum, anidulafungin was the most active compound but 10 and 20% serum abrogated the efficacy of all three echinocandins. Established biofilm cultures that included both the nonadherent and adherent phases were more resistant to micafungin than caspofungin regardless of serum concentration, while anidulafungin had significant activity at 1 and 5% serum concentrations. Nascent biofilms were mostly affected by anidulafungin in 1 and 5% serum, but none of the compounds showed significant activity in 20% serum. We show for the first time that (i) echinocandins differ in their abilities to deplete the ATP of Pneumocystis in biofilms and in suspension cultures, (ii) this variability mostly reflected the reported efficacies in animal models of infection, and (iii) high serum levels decreased the anti- Pneumocystis activities of the echinocandins in both in vitro systems.
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Members from Acremonium, Aspergillus, Cladosporium, Fusarium, and Pneumocystis, in addition to Candida, are among the biofilm formers tested for drug susceptibility in vitro.
“These include (in addition to Candida) members from Acremonium, Aspergillus, Cladosporium, Fusarium, and Pneumocystis (9, 20, 35, 42, 79, 160, 176).”
From <i>Candida albicans</i> Biofilms and Human Disease (2015) · cites this paper as [35]
Cells in biofilms have been found to be more resistant to drugs compared with cells grown in suspension culture.
“For example, a number of these biofilm formers (Table 3) have been tested for drug susceptibility in vitro, and cells in biofilms have been found to be more resistant to drugs compared with cells grown in suspension culture.”
From <i>Candida albicans</i> Biofilms and Human Disease (2015) · cites this paper as [35]
Morphological examination of lung tissue infected by Pneumocystis jirovecii reveals a biofilm-like growth structure consisting of round yeast-form clusters that can be recapitulated in vitro under certain laboratory conditions.
“Morphological examination of lung tissue infected by P. jirovecii reveals a biofilm-like growth structure consisting of round yeast-form clusters that can be recapitulated in vitro under certain laboratory conditions (35, 36).”
From <i>Candida albicans</i> Biofilms and Human Disease (2015) · cites this paper as [35]
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Self-citation
- Authors
- Cushion, M. T., & Collins, M. S.
- Affiliations
- Cincinnati VA Medical Center (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2011-10
- Volume
- 55
- Issue
- 10
- Pages
- 4513-4518
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3186961
- OpenAlex
- W2058633046
- Cited by
- 38
- References
- 38
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (N01-A1-25647)
- National Institute of Allergy and Infectious Diseases (R01AI076104)
- Topics
- Health Sciences › Medicine › Epidemiology › Pneumocystis jirovecii pneumonia detection and treatment
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Pneumocystis carinii, Pneumocystis murina, echinocandins, anidulafungin, caspofungin, micafungin, Pneumocystis carinii pneumonia, serum resistance, ATP depletion, cyst development, antifungal susceptibility
- MeSH terms
- Caspofungin, Micafungin, Anidulafungin, Adenosine Triphosphate, Animals, Antifungal Agents, Microbial Sensitivity Tests, Pneumocystis Infections, Biofilms, Drug Resistance, Fungal, Pneumocystis carinii, Rats, Echinocandins, Lipopeptides
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